Nitrophenyl carbamic acid esters as molluscicides



United States Patent "ice NITROPI-IENYL CARBAMIC ACID ESTERS ASMOLLUSCICIDES Rudolf Heiss, Cologne-Stammheim, and Ernst Grigat,

Ernst Becker, and Gunther Hermann, Leverkusen, Germany, assignors toFarbenfabriken Bayer Aktiengesellschaft, Leverkusen, Germany, acorporation of Germany No Drawing. Original application Mar. 3, 1965,Ser. No.

436,916, now abandoned. Divided and this application Feb. 16, 1967, Ser.N0. 632,852 Claims priority, application Germany, Mar. 5, 1964,

Int. Cl. A01n 9/2 0; C07c 125/06 U.S. Cl. 424-300 12 Claims ABSTRACT OFTHE DISCLOSURE Methods of controlling molluscs by applying to themolluscs and/or their habitat a molluscicidally elfective amount of anitrophenyl carbamic acid ester having the formula in which R is loweralkyl, R and R' each is hydrogen or lower alkyl, R" is lower alkyl,halo-substituted lower alkyl, phenyl, or halo-substituted phenyl, andeach A is hydrogen or nitro, at least one such A being nitro.

This is a divisional application of copending application Ser. No.436,916, filed Mar. 3, 1965, now abandoned.

The present invention is concerned with new carbamic acid esters, andcompositions containing the same, having a molluscicidal activity andwith methods for the production and use thereof. a

It is already known that some carbamic acid esters have a molluscicidalactivityz' 3,5-dimethy1-4-dimethyl-aminophenyl- I-methyl carbamate isregarded as particularly active (Arnold: Snail and lawn pest controlwith Zectran pesticide, Down to Earth, 18, No. 3, pp. -24).

It is an object of the present invention to provide particular carbamaicacid esters which exhibit highly effective molluscicidal properties.

It is another object of the present invention to provide processes forthe production .of such particular carbamic acid esters utilizingvarious starting materials whereby a versatile overall technique may beused to produce the particular carbamic acid esters of the foregoingtype, depending upon the availability of various starting materials andthe desirability of carrying out the production process by oneparticular route rather than another.

It is another object of the present invention to provide compositionscontaining such carbamic acid esters, which possess such activity, aswell as methods for using such esters to combat mollusks.

It is still another object of the present invention to provide variousprocesses for the production of such carbamic acid esters utilizing anextremely wide tempera- 3,458,639 Patented July 29, 1969 ture range forsuch purpose in the presence or absence of solvents or reactiondiluents.

It is a further object of the present invention to provide particularcarbamic acid ester compounds which possess a low toxicity to warmblooded animals and fish yet which at the same time exhibit strongmolluscicidal properties, for particular control of both land and waterpulmonate gastropods.

It is still another object of the present invention to providecompositions or formulations of the aforesaid carbamic acid esters withcarrier vehicles.

Other and further objects of the present invention will become apparentfrom a study of the within specification and accompanying examples.

It has now been found in accordance with the present invention thatnitro phenyl carbamic acid esters of the general formula:

l t'ii wherein R, R and A have the foregoing meaning, is reacted with anisocyanate of the general formula wherein R" has the foregoing meaning;or (b) when a phenol of general Formula II is first converted with anexcess of phosgene into the corresponding chloroformic acid ester andsuch chloroformic acid ester is then reacted with an alkylamine of thegeneral formula:

H-b'I-R" (III) wherein R" and R" have the foregoing meaning; or (c) whena phenol of general Formula II is first reacted with an approximatelyhalf molar quantity of phosgene to form the corresponding bis-(phenyl)carbonate and such bis-(phenyl) carbonate is then reacted with analkylamine of general Formula III.

In the above-noted general Formula I, R preferably represents an alkylradical containing 1 to 5 carbon atoms, R" preferably represents analkyl radical containing 1 to 5 carbon atoms or a phenyl radical, theradical R" possibly being substituted by halogen, such as chlorine and/or bromine, and R and R'", which may be the same or When3,5-dimethyl-4-nitro-phenol and methyl isocyanate are used as startingmaterials for the instant process, the sequence of the reactionaccording to method (a) may be represented by the following equation:

omQon CON-OH;

The reaction may be carried out in an inert solvent, if desired.Hydrocarbons, including aliphatic and aromatic hydrocarbons, such asbenzine (petroleum fraction boiling at 70-90 C.) and benzene, toluene,xylene, mesitylene, etc., may, for example, be used for this purpose, aswell as ethers, especially cyclic ethers, such as furan, dioxan, etc. Itis, however, also possible to react the components directly in theabsence of solvents. The reaction is accelerated by the addition of atertiary amine, such as a trilower alkyl amine having 1-4 carbon atomsper alkyl chain, for example, triethylamine. The reaction temperaturesmay be varied within a fairly wide range. In general, the operation iscarried out at a temperature substantially between about and 150 C.

Method (b) When 3,5-dimethyl-4-nitro-phenol and methylamine are used asstarting materials, the sequence of the reac tion during the secondstage of method (b), i.e. after the condensation reaction between suchphenol compound and phosgene in the first stage, can be represented bythe following equation:

During the first stage, the nitrophenol is converted by an excess ofphosgene into the corresponding chloroformic acid ester, conveniently ifdesired in the presence of inert solvents, such as aromatichydrocarbons, i.e. benzene, toluene, xylene, mesitylene, etc. A base,conveniently an alkali metal hydroxide, e.g. sodium, potassium orlithium hydroxide, is continuously added dropwise in order to neutralizethe hydrochloric acid formed. The pH value, however, should remain at6-7. The reaction temperatures may be varied within a fairly wide range.In general, the operation is carried out at a temperature substantiallybetween about 10 and +10 C.

During the second stage, the chloroformic acid ester is reacted with anapproximately equivalent quantity of the amine. For this purpose, ifdesired, it is convenient to operate in the presence of inert solvents,such as aro- '4 matic and aliphatic hydrocarbons, such as benzene,toluene, xylene, mesitylene, etc., benzine, etc., as well as ethers,especially cyclic ethers such as furan, dioxan, etc. The reactiontemperatures may again be varied within a certain range: in general,they are substantially between about -10 and +10 C.

Method (c) [OzN- During the first stage, the nitrophenol is of coursereacted with an approximately half molar quantity of phosgene. Ifdesired, it is convenient to carry out this operation in the presence ofan inert solvent. A base, preferably an alkali metal hydroxide, e.g.sodium, potassium or lithium hydroxide, is added in order to neutralizethe hydrochloric acid formed. The pH value is maintained preferably atsubstantially about 8. The temperatures may again be varied within afairly wide range but preferably is substantially between about 20 and60 C.

The bis-nitrophenyl carbonate formed during the first stage is reactedwith the amine. It is convenient, if desired, to carry out thisoperation without the use of a solvent. The most favorable reactiontemperatures are substantially between about -l0 and +20 C.

The nitro-alkyl-phenols used as the starting materials, in accordancewith the present invention, some of which are new, can be obtained bythe nitration of the corresponding phenols and subsequent separation ofthe oisomers by steam distillation.

The compounds according to the present invention have a low toxicitytoward warm-blooded animals and fish but, nevertheless, exhibit strongmolluscicidal properties and are, therefore, suitable for the control ofgastropods such as land pulmonate gastropods (Styllommatophora) andwater pulmonate snails (Basommatophora).

The land pulmonate gastropods (slugs and snails) mainly include theZonitidae, such as Oxychilus drapamaldi; the Limacidae,' such asDeroceras reticulatum and Deroceras agreste; the Arionidae, such asArion rufus; the Endodontidae, such as Goniodiscus rotundatus; and theHelicidae, such as Fruiticicola hispida, T Izeba pisana, Arianta arbusto rum and Cepaea memoralis. U

The water pplmonate snails mainly comprise the Limnaeidae, such asLz'mnaea t runcatul a; and the Planorbidae, such as Helispma nigricans,

The newcompounds according tothe present inven; tion can be utilized, ifdesired, in the form of the usual formulations or compositions withdispersible carriervehicles, such as emulsifiable concentrates, spraypowders,

, pastes, soluble powders, dusting agents, etc., and especialpurpose:solvents, such as aromatic hydrocarbons (for example, toluene, xylene orbenzene, etc.), chlorinated aromatic hydrocarbons (for example,chlorobenzene), paraflins (for example, petroleum fractions), alcohols(for example, methanol, propanOl or butanol, etc.), amines (for example,ethanolamine), dimethyl-formamide, and water; finely divided solidcarriers, such as natural ground minerals (for example, kaolins,alumina, talc, SiO and chalk) and synthetic ground minerals (forexample, highly-dispersed silicic acid and silicates, e.g. alkalisilicates, etc.); emulsifying agents, such as nonionic and anionicemulsifying agents (for example, polyethylene oxide esters of fattyacids, polyethylene oxide ethers of fatty alcohols, alkyl sulfonates andaryl sulfonates, especially magnesium stearate, sodium oleate, etc.);and dispersing agents, such as lignin, spent sulphite liquors and methylcellulose, as well as natural and synthetic attractant agents and baits,such as milled cereal products, bran, egg powder, ground dried blood,casein, dried yeast and ethereal oils.

The active compounds according to the present invention may also bepresent in the compositions in the form of mixtures with knownmolluscicidal agents, if desired, such as metaldehyde.

In general, the compositions or formulations contain substantiallybetween about 0.1 and 95 percent by weight of the active agent,preferably substantially between about 0.5 and 90 percent andparticularly between substantially about 0.5- percent, by weight.

The compounds according to the present invention, their compositionswith carrier vehicles or other active agents, and their preparations inthe form of particular dosages for specific application are used forspraying and dusting the soil and plants and they may also be applied inthe form of granulates or as baits or used for fumigation, for example,in greenhouses. They can also be added to water in a suitable form, suchas in the form of an emulsifiable concentrate, granulate or solublepowder, as for example for the control of water snails.

The following Examples are given for the purpose f illustration, and notlimitation, of the present invention;

Example A 0.167 g. of a tale preparation containing 30% 4-nitro- 3,5dimethyl phenyl N methyl carbamate were mixed with 3.833 g. fine wheatbran. The concentration of the active agent thus amounted to 1.25%. Thismixture was applied uniformly on the inner surfaces of a glass Petridish of cm. diameter which had been lined with moist filter papers.

Two red slugs (Arion nufus) were placed into this dish. Both of thesewere dead on the second day of the experiment. Untreated controls stilllived after seven days, when the experiment was finished.

Example B Two specimens of the slug Limax flavus were placed in a Petridish prepared as in Example A; these died n the second day of theexperiment whereas the untreated controls (see Example A) still livedafter seven days.

Example C A pulp was prepared from 55% fine wheat bran, 10% dried wholeegg powder, 5% ground dried blood, 5% methyl cellulose, 10% casein, 10%dried yeast and 5% 4 nitro 3,5 dimethyl phenyl N methyl carbamate, withthe addition of some water, and this dried again and then granulated. 2g. of this granulated bait were spread uniformly on one-half of thefloor area of a wire gauze box (dimensions 25 x 25 x 10 cm.) which hadbeen covered with soil; the other half was left untreated. A youngcabbage plant was placed in each corner of the box. Four fully grownspecimens of the red slug (Arion rufus) were placed on the untreatedside. Two

of the slugs had died by the third day of the experiment and the othertwo slugs were dead on the fourth day. The cabbage plants remainedunaffected. An untreated control group still lived after an observationperiod of seven days.

Example D The whole area of an experimental box of the type described inExample C was dusted with 5 g. of a powder consisting of 5% 4 nitro 3,5dimethyl phenyl N- methyl carbamate and finely-dispersed silicondioxide. Four red slugs (Arion rufus) were again introduced and all ofthese died on the third or fourth day of the experiment. An untreatedcontrol group still lived after an observation period of seven days.

Example E 1 g. of a bait mixture consisting of 5%4-nitro-3,5-dimethyl-phenyl-N-methyl carbamate, 94.5% fine wheat branand 0.5% of a mould prevention product was placed on one-half of thefloor area of an experimental box of type described in Example C. Theother half was again left untreated and four red slugs (Arion rufus)were placed on it. One of the animals died on the second day, another onthe third day and the last two on the fourth day of the experimentwhereas the untreated controls (see Example C) survived for the fullseven day observation period remaining healthy.

Example F 50 mg. 4-nitro-3,S-dimethyl-phenyl-N-methyl carbamate weredissolved, by warming, in 300 mg. of a polyoxyethylene glycolsul'fonate, with the addition of 1 ml. acetone, and then diluted to 1litre with aquarium water. 10 water pulmonate snails (Helisomanigricans) were then introduced into this mixture containing 50 ppm. ofthe active agent. All the animals were dead after 3 hours.

Example G The following Table 1 summarizes the results of seven dayexperiments carried out in accordance with Example E with the red slugArion rufus to illustrate the improved activity of the new carbam-atesaccording to the present invention compared with those presently known.The carrier was the same as described in Example E.

Example H Table 2 summarizes the results of a comparative seven dayexperiment carried out in accordance with Examples A and B on the cellarslugs (Limax flavus). The carrier was the same as described in ExamplesA and B.

TABLE 2 Number of experi- Time mental required Concenspecimens rdetration, (Limaz Mortality, struction, Product in percent flav'us) inpercent days (1) 4 nitro-3,5-

dimethyl-phenyl-N- methyl carbamate 1. 25 2 2-3 (2) N-methyl-lnaphthylcarbamate (known 1. 25 2 0 Example I 16.7 g. (0.1 mole)3,5-dimethyl-4-nitro-phenol are dissolved in dioxan and reacted with6.27 g. (0.11 mole) methyl isocyanate. The reaction mixture becomesslightly warm when 3 drops triethylamine have been added. It is heatedat 45 C. for another 30 minutes and left to stand overnight, in order tocomplete the reaction. The solvent is distilled off in vacuo, ahoney-colored oil remaining which crystallizes completely ontrituration. When recrystallized from alcohol,3,S-dimethyl-4-nitrophenyl-N- methyl carbamate is obtained with amelting point of 111 C.

3 methyl--ethyl-4-nitrophenyl-N-methyl carbamate, 3-isopropyl 4nitrophenyl-N-methyl carbamate, and 3,5-dimethyl 2 nitrophenyl-N-methylcarbamate, can be prepared according to the same method, as well asother analogous products:

M.P. 79 C.

O I O--NHCH; M.P. 134 C.

CH; No,

Example .II

Example I may be repeated under substantially the same conditionsstarting with other alkyl isocyanates, such as methyl-, ethyl-,isopropyl-, and butyl, isocyanates, respectively and appropriatenitrophenols such as 3,5-dimethyl 4 nitrophenol,3,S-dimcthyl-Z-nitrophenol, 3- isopropyl 4 nitrophenol, 3methy1-5-ethyl-4-nitrophenol, 3-ethyl 5 n-propyl-4-nitrophenol,3-n-butyl-5- isobutyl-2,4-dinitrophenol, and 3-propyl 2 nitrophenol,respectively, whereby corresponding carbamic acid esters are obtained,all of which possess the desired molluscicidal activity, especially indosage concentrations of substantially between about 1.25 to 5%.

Prefer-ably, R in the foregoing formulae represents lower alkyl, such asC -C lower alkyl inclusive, and particularly a member selected from thegroup consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl,isobutyl, sec.-butyl, and tert.-butyl, etc.; R in the foregoing formulaerepresents hydrogen or R as defined immediately hereinabove; R" in theforegoing formulae represents R as defined immediately hereinabove; R inthe foregoing formulae represents hydrogen; and one A in the foregoingformulae represents hydrogen and the other A in the foregoing formulaerepresents NO Thus, such compounds include the following types:

It will be appreciated that the instant specification and examples areset forth by way of illustration and not limitation, and that variousmodifications and changes may be made without departing from the spiritand scope of the present invention.

What is claimed is:

1. Method of controlling molluscs which comprises applying to themolluscs and their habitat a molluscicidally effective amount of anitrophenyl carbamic acid ester of the formula in which, R is a loweralkyl radical having 1-5 carbon atoms, R and R' each is selected fromthe group consisting of hydrogen and a lower alkyl radical having 1-5carbon atoms, R" is selected from the group consisting of a lower alkylradical having 1-5 carbon atoms, and a phenyl radical, and each A isselected from the group consisting of hydrogen and a nitro group, atleast one such A being a nitro group.

2. Method according to claim 1 wherein said ester is used in aconcentration of between substantially about 05-10% in a dispersiblecarrier vehicle selected from the group consisting of solvents; finelydivided solids; mixtures of solvents with a member selected from thegroup consisting of non-ionic and anionic emulsifying agents dispersingagents, and mixtures of such agents; mixtures of solvents with a memberselected from the group consisting of natural and synthetic attractantagents and baits; and mixtures of finely divided solids with a memberselected from the group consisting of natural and synthetic attractantagents and baits.

3. Method according to claim 1 wherein R is a lower alkyl radical having1-5 carbon atoms, R is hydrogen, R" is a lower alkyl radical having 1-5carbon atoms, R' is hydrogen, and one A is hydrogen and the other A is anitro group.

4. Method according to claim 1 wherein R is a lower alkyl radical having1-5 carbon atoms, R is a lower alkyl radical having 1-5 carbon atoms, R"is a lower alkyl radical having 1-5 carbon atoms, R" is hydrogen, andone A is hydrogen and the other A is a nitro group.

5. Method according to claim 1 wherein said ester has the formula o -oialkyl 0 Cir-C4 alkyl I; OzN 0- -N \H C1-C4 alkyl C1-C4 alkyl 9. Methodof controlling molluscs which comprises applying to the molluscs andtheir habitat a molluscicidally effective amount of3,5-dimethyl-4-nitrophenyl-N-methyl carbamate of the formula 10. Methodof controlling molluscs which comprises applying to the molluscs andtheir habitat a molluscicidally eflFective amount of3-methyl-5-ethy1-4-nitrophenyl-N- methyl carbamate of the formula 1LMethod of controlling molluscs which comprises applying to the molluscsand their habitat a molluscicidally effective amount of3-isopropyl-4-nitrophenyl-N-methyl carbamate of the formula CH3CH-GH3 oO.N@ O r 12. Method of controlling molluscs which comprises applying tothe molluscs and their habitat a molluscicidally effective amount of3,5-dimethyl-2-nitrophenyl-N-methyl carbamate of the formula ReferencesCited UNITED STATES PATENTS 2,933,383 4/ 1960 Lambrech. 3,265,567 8/1966Rice et al. 16738.6

FOREIGN PATENTS 128,292 5/1950 Sweden. 554,576 3/ 1958 Canada. 1,139,11311/1962 Germany.

OTHER REFERENCES Kolbezen et al., Journal of Agricultural & FoodChemistry, vol. 2, pp. 864-870, 1954.

FRANK CACCIAPAGLIA, 1a., Primary Examiner VINCENT D. TURNER, AssistantExaminer @2 3 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTIONPatmuzNo. 3,458,639 Datmi July 1969 lnventofls) Rudolf Heiss, ErnstGrigat, Ernst Becker and Gunther Hermann It is certified that errorappears in the above-identified patent and that said Letters Patent arehereby corrected as shown below:

[ Column 7, line 70, in the structural formula "C -C should read -C CSIGNED ANU SEALED DESZ w (SEAL) Aucst:

Flmlm mm E. sum, JR. Anesting Officer OOIIniBsioner of Patents

